CYT387

A potent and selective JAK1/JAK2 inhibitor with IC50 of 11/18 nM; shows significantly less activity against other kinases, including JAK3 (IC50=155 nM) ; inhibits JAK2V617F (JH1-JH2) withIC50 of 11 nM; inhibits growth of Ba/F3-JAK2V617F and HEL cells (IC50=1500 nM) or Ba/F3-MPLW515L cells (IC50=200 nM) . Bone Cancer Phase 3 Clinical (In Vitro) :Momelotinib (CYT387) inhibits the proliferation of parental Ba/F3 cells (Ba/F3-wt) stimulated by IL-3 with IC50 of 1400 nM. Furthermore, Momelotinib (CYT387) also causes the inhibition of cell proliferation in cell lines constitutively activated by JAK2 or MPL signaling, including Ba/F3-MPLW515L cells, CHRF-288-11 cells and Ba/F3-TEL-JAK2 cells with IC50 of 200 nM, 1 nM and 700 nM, respectively. In addition, Momelotinib (CYT387) has been shown to inhibit erythroid colony growth in vitro from JAK2V617F-positive PV patients with similar potency with IC50 of 2 μM-4 μM. Momelotinib (CYT387) inhibits PI3K/AKT and Ras/MAPK signaling induced by IL-6 and IGF-1. Moreover, Momelotinib (CYT387) induces apoptosis as a single agent and synergizes with the conventional anti-MM therapies PS-341 and L-PAM in primary multiple myeloma (MM) cells. (In Vivo) :In a murine MPN model, Momelotinib (CYT387) normalizes white cell counts, hematocrit, spleen size, and restores physiologic levels of inflammatory cytokines.